The purpose of this review is to increase the awareness of internal carotid artery dissection (ICAD), a potentially serious and probably underdiagnosed condition. ICAD is a not uncommon cause of stroke in young patients. ICAD may occur spontaneously or as a result of trauma. However, the "spontaneous" dissection is often preceded by a trivial trauma. The typical patient presents with ipsilateral headache or neck pain, ipsilateral Horner's syndrome and delayed ischemic symptoms from the ipsilateral hemisphere or retina. Conventional angiography, the gold standard for diagnosis, tends to be replaced by non-invasive diagnostic methods. There are no evidence-based guidelines for therapy although anticoagulation is most commonly used. The references are selected from the Medline database for the years 1966-1997.
Gliomas are brain tumors characterized by an immunosuppressive microenvironment. Immunostimulatory agonistic CD40 antibodies (αCD40) are in clinical development for solid tumors, but are yet to be evaluated for glioma. Here, we demonstrate that systemic delivery of αCD40 in preclinical glioma models induces the formation of tertiary lymphoid structures (TLS) in proximity of meningeal tissue. In treatment-naïve glioma patients, the presence of TLS correlates with increased T cell infiltration. However, systemic delivery of αCD40 induces hypofunctional T cells and impairs the response to immune checkpoint inhibitors in pre-clinical glioma models. This is associated with a systemic induction of suppressive CD11b+ B cells post-αCD40 treatment, which accumulate in the tumor microenvironment. Our work unveils the pleiotropic effects of αCD40 therapy in glioma and reveals that immunotherapies can modulate TLS formation in the brain, opening up for future opportunities to regulate the immune response.
Background and Purpose-An increase in intima-media thickness (IMT) in the common carotid artery (CCA) is commonly used as a marker of atherosclerosis. The purpose of this study was to investigate the relationship between IMT in the CCA and atherosclerosis in the carotid bifurcation. Methods-182 consecutive patients (mean age, 67 years) referred for carotid duplex scanning were included. We measured IMT and classified plaques by means of a high-resolution ultrasound technique. Results-IMT was correlated to age, male gender, ischemic heart disease, and presence of plaques or stenoses in any of the carotid bifurcations. In men, IMT was larger on the left than on the right side. Plaques were seen in 163 carotid bifurcations, in 45 of these with Ͼ50% stenosis. On the left side but not on the right, there was a correlation between IMT in the CCA and presence of plaques or stenoses in the carotid bifurcation. Echogenic plaques were more common than echolucent, but the latter caused significantly more stenoses. No relationship was found between plaque echogenicity and IMT. Conclusions-IMT of the CCA is correlated to the degree of atherosclerosis in the carotid bifurcations in general and on the left side also to the presence of plaques or stenoses in the left carotid bifurcation. Our results support earlier observations suggesting faster development of carotid atherosclerosis on the left than on the right side. Echogenic plaques were more common and generally smaller than echolucent plaques, but there was no correlation between plaque echogenicity and IMT. (Stroke. 1998;29:1378-1382.)
Human cytomegalovirus (HCMV) has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC) methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.
OBJECTIVE Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed. METHODS Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices. RESULTS Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H-positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences. CONCLUSIONS The authors present a new method for the coregistration of histological and radiological characteristics of en bloc-removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.
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